function, and biomedical application of mammalian extracellular vesicles that are
categorized into exosomes and ectosomes (also known as microvesicles). We also
discuss on perspectives for a future comprehensive understanding of extracellular
vesicle-mediated pathophysiological functions, decoding the secrets of life, as well
as developing novel extracellular vesicle-based diagnostics and therapeutics against
hard-to-cure diseases: isolation of extracellular vesicles, extracellular vesiclemimetic nanovesicles as novel alternatives to extracellular vesicle-based therapeutics, and a holistic systems biology approach based on the concept of emergent
properties.
6.1 Introduction
Extracellular vesicles (EVs) are nano-sized bilayered spherical proteolipids
encapsulating various cellular components [1–11]. Cells of all domains of life on
earth actively release these vesicles to the extracellular environment including
various biological fluids. EVs are endogenous and environmental nanocarriers of
specific subsets of cellular bioactive molecules including proteins, lipids, mRNAs,
miRNAs, and metabolites (Fig. 6.1). Growing evidence in this emerging field has
shown that EVs are involved in intercellular, inter-species and inter-kingdom
communications: collectively, EV-mediated communication is evolutionarily conserved phenomenon.
Despite recent explosively increased interest regarding their components, biogenesis, and pathophysiological functions as well as biomedical application
(Fig. 6.2), EVs are first observed, in the middle of 20th century, without recognition
of their physiological roles and evolutionally conserved cell biological properties.
Briefly, in 1946, platelet-derived particles were first observed from normal human
plasma [12] and designated them as “platelet dust” [13]. Later on, other investigators independently observed EVs and referred them differently such as matrix
vesicles during calcification process [14] and prostasomes present in seminal
plasma [15, 16]. In 1981, Dvorak and colleagues reported that cancer cells shed
plasma membrane vesicles that carry procoagulant activity [17].
In 1983, studies on the biogenesis and physiological functions of EVs were
reported and detailed ultrastructural studies showed that vesicles formed in multivesicular bodies are released by fusion of multivesicular bodies with the cell
membrane during the maturation of red blood cells [18, 19]. In 1996, these types of
EVs known as exosomes isolated from B lymphocytes exhibited their
antigen-presenting function in T cell responses [20]. Moreover, in 2002, Kim and
colleagues reported, for the first time, that sphingomyelin present in cancer
cell-derived EVs plays a critical role in angiogenesis, the new blood vessel formation from pre-existing vasculature [21].
In 2007, discovery of EV-mediated lateral gene transfer, where mRNA in EVs
from donor cells were translated in recipient cells [22], have led intensive studies
focusing on EVs as genetic carriers able to modulate pathophysiological status of
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C. Lee et al.
categorized into exosomes and ectosomes (also known as microvesicles). We also
discuss on perspectives for a future comprehensive understanding of extracellular
vesicle-mediated pathophysiological functions, decoding the secrets of life, as well
as developing novel extracellular vesicle-based diagnostics and therapeutics against
hard-to-cure diseases: isolation of extracellular vesicles, extracellular vesiclemimetic nanovesicles as novel alternatives to extracellular vesicle-based therapeutics, and a holistic systems biology approach based on the concept of emergent
properties.
6.1 Introduction
Extracellular vesicles (EVs) are nano-sized bilayered spherical proteolipids
encapsulating various cellular components [1–11]. Cells of all domains of life on
earth actively release these vesicles to the extracellular environment including
various biological fluids. EVs are endogenous and environmental nanocarriers of
specific subsets of cellular bioactive molecules including proteins, lipids, mRNAs,
miRNAs, and metabolites (Fig. 6.1). Growing evidence in this emerging field has
shown that EVs are involved in intercellular, inter-species and inter-kingdom
communications: collectively, EV-mediated communication is evolutionarily conserved phenomenon.
Despite recent explosively increased interest regarding their components, biogenesis, and pathophysiological functions as well as biomedical application
(Fig. 6.2), EVs are first observed, in the middle of 20th century, without recognition
of their physiological roles and evolutionally conserved cell biological properties.
Briefly, in 1946, platelet-derived particles were first observed from normal human
plasma [12] and designated them as “platelet dust” [13]. Later on, other investigators independently observed EVs and referred them differently such as matrix
vesicles during calcification process [14] and prostasomes present in seminal
plasma [15, 16]. In 1981, Dvorak and colleagues reported that cancer cells shed
plasma membrane vesicles that carry procoagulant activity [17].
In 1983, studies on the biogenesis and physiological functions of EVs were
reported and detailed ultrastructural studies showed that vesicles formed in multivesicular bodies are released by fusion of multivesicular bodies with the cell
membrane during the maturation of red blood cells [18, 19]. In 1996, these types of
EVs known as exosomes isolated from B lymphocytes exhibited their
antigen-presenting function in T cell responses [20]. Moreover, in 2002, Kim and
colleagues reported, for the first time, that sphingomyelin present in cancer
cell-derived EVs plays a critical role in angiogenesis, the new blood vessel formation from pre-existing vasculature [21].
In 2007, discovery of EV-mediated lateral gene transfer, where mRNA in EVs
from donor cells were translated in recipient cells [22], have led intensive studies
focusing on EVs as genetic carriers able to modulate pathophysiological status of
128
C. Lee et al.